New Tests and Treatments May Help People With AATD-Related Liver Disease

Rohit Loomba, MD, MHSc

A recent review article is helping doctors learn more about new advancements in the treatment and diagnosis of liver disease caused by alpha-1 antitrypsin deficiency (AATD).¹ The review comes from a meeting of experts who specialize in AATD-related liver disease. They looked at current research to better understand the disease, identify new markers in the body called biomarkers, and explore ideas for new drug treatments.

Rohit Loomba, MD, MHSc, from the University of California at San Diego, and his colleagues emphasized that this kind of meeting helps the medical community come together and work toward improving the lives of people with AATD liver disease.

AATD mostly affects people of Northern or Central European descent and impacts about 100,000 people in the U.S. However, many people with AATD don’t know they have it because it’s often not diagnosed. Only around 10% of those with AATD have received a diagnosis.²

AATD-related liver disease happens when a faulty version of a protein called Z-AAT builds up in the liver, causing damage to the cells. Over time, this can lead to scarring, cirrhosis, liver transplants, or even death. The Pi*ZZ gene increases the chance of serious liver disease, while the Pi*MZ gene can make other liver diseases worse.

Compared to AATD lung disease, it is even harder to diagnose AATD-related liver disease early. This can lead to worse outcomes for patients. There are several reasons for this, such as low awareness of the disease, not enough testing, and the fact that mild liver disease often doesn’t have many symptoms. A liver biopsy, which is a test that involves removing a small piece of the liver for examination, is usually needed to confirm the diagnosis.

Researchers are trying to find better ways to identify people with the Pi*ZZ gene who might develop AATD liver disease. They’ve found that being male, over 50 years old, having abnormal liver tests, being infected with hepatitis, being obese, having metabolic syndrome, and having diabetes all increase the risk of developing AATD liver disease. However, more work is needed to identify people who are at risk so that doctors can test them early.

Right now, there aren’t many good tests to find or track AATD liver disease. The gold standard is a liver biopsy, but this procedure is invasive, expensive, and has risks. The results can also vary depending on how the pathologist interprets them, which can make the results less reliable.

The review discussed the possibility of using automated image analysis, powered by artificial intelligence, to get more accurate and consistent results from liver biopsies. This technology could help reduce the variation between pathologists and make the results of clinical trials more reliable. However, this method hasn’t been approved yet.

Researchers are also exploring blood tests to track liver disease. One promising development is measuring liver stiffness, a noninvasive test that appears to be safe and reliable.

Although augmentation therapy is a standard treatment for AATD lung disease, it does not help with AATD liver disease. New treatments are being developed, but progress is slow due to the challenges of studying rare diseases like AATD liver disease. Despite these challenges, experts believe that learning from other liver diseases could help speed up the process of finding effective treatments.

An original version of this article was published on sister site HCPLive.

References:

1. ^{Loomba R, Clark G, Teckman J, et al. Review article: New developments in biomarkers and clinical drug development in alpha-1 antitrypsin deficiency-related liver disease. Aliment Pharmacol Ther. 2024;59(10):1183-1195. doi:10.1111/apt.17967.}
2. ^{NORD. Alpha-1 antitrypsin deficiency - symptoms, causes, treatment: Nord. National Organization for Rare Disorders. March 22, 2024. Accessed May 31, 2024. https://rarediseases.org/rare-diseases/alpha-1-antitrypsin-deficiency/#complete-report.}